Effects of bromohomoibotenate on metabotropic glutamate receptors

Neuroreport. 1994 Dec 20;5(18):2417-20. doi: 10.1097/00001756-199412000-00003.

Abstract

(S)-Bromohomoibotenic acid [(S)-BrHIbo] stereoselectively antagonized glutamate-stimulated phosphoinositide (PI) hydrolysis in baby hamster kidney (BHK) cells expressing mGluR1a in a competitive manner with an IC50 of 250 microM. However, (S)-BrHIbo did not inhibit (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced PI hydrolysis in rat hippocampal slices (S)- or (R)-BrHIbo did not show any effects on forskolin-stimulated cAMP-formation in BHK cells expressing mGluR2 or mGluR4 but did displace [3H]2-amino-4-phosphonobutyrate ([3H]AP4) binding from rat corticalmembranes with high affinities (IC50 = 1.0 microM and 1.1 microM, respectively). These data suggest that (S)-BrHIbo may interest with multiple PI-coupled glutamate receptors, however, at concentrations that are several fold higher than for displacement of [3H]AP4 binding from rat cortical membranes.

MeSH terms

  • Aminobutyrates / metabolism
  • Animals
  • Binding, Competitive
  • Cell Line
  • Cerebral Cortex / metabolism
  • Cricetinae
  • Cyclic AMP / metabolism
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Dose-Response Relationship, Drug
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Hippocampus / metabolism
  • Hydrolysis / drug effects
  • Ibotenic Acid / analogs & derivatives*
  • Ibotenic Acid / chemistry
  • Ibotenic Acid / metabolism
  • Ibotenic Acid / pharmacology
  • Kidney / cytology
  • Kidney / metabolism*
  • Membranes / metabolism
  • Phosphatidylinositols / metabolism
  • Quinoxalines / pharmacology
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / classification
  • Receptors, Metabotropic Glutamate / drug effects*
  • Receptors, Metabotropic Glutamate / metabolism*
  • Stereoisomerism

Substances

  • Aminobutyrates
  • Phosphatidylinositols
  • Quinoxalines
  • Receptors, AMPA
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • 4-bromohomoibotenic acid
  • Ibotenic Acid
  • Glutamic Acid
  • Cyclic AMP
  • 2-amino-4-phosphonobutyric acid